1h AND 31p magnetic resonance spectroscopy (MRS) can examine metabolic processes in living patients. 31P MRS provides information on high- energy phosphate (adenosine triphosphate [ATP], inorganic orthophosphate [Pi] and phosphocreatine[Pcr]), phospholipid membrane metabolism (phosphomonoester [PME] and phosphodiesters [PDE]), Ph and intracellular Mg++ in regions as small as 15 cc. 1H MRS can quantify glutamate, N- acetylaspartate (NAA), glutamine, aspartate, gamma-aminobutyrate (GABA) and choline in regions as small as 4 cc. It is not presently possible to examine any of these compounds with other imaging techniques. Studies with these techniques in schizophrenia are very limited to date. However, our preliminary 1H and 31P MRS data suggest that schizophrenic patients have markedly lower PME and glutamate levels and higher PDE, intracellular Mg++ and Pcr levels in the left prefrontal region compared to normals. Unlike other brain imaging techniques, there was no overlap between groups on intracellular Mg++ and glutamate levels and almost no overlap on PME levels. PDE levels were higher in early cases, possible indicating a degenerative process, as these compounds are associated with cell membrane breakdown. We think that these findings provide the first in vivo evidence for the involvement of glutamate in schizophrenia. We propose to replicate the Mg++ and glutamate findings and extend our regions of interest to the left orbitomedial and right dorsolateral prefrontal, left and right mesial-temporal and left lenticular regions. We also propose to determine the specificity of these findings to schizophrenia by examining other patient groups. Volumetric and family history correlations will be examined as well. We believe that these studies could have important implications for the pathophysiology of schizophrenia.